Institute of Cell Biology (Cancer Research), University Hospital Essen, Germany.
Radiother Oncol. 2011 Oct;101(1):86-92. doi: 10.1016/j.radonc.2011.05.064. Epub 2011 Jun 29.
Pneumonitis and fibrosis constitute dose-limiting side effects of thorax or total body irradiation. An improved understanding of the underlying mechanisms is a prerequisite for the development of effective radioprotective strategies. Here we characterized the behavior of resident and immune cells in a murine model of radiation-induced pneumopathy.
Wild type (WT) or RAG-2 deficient C57BL/6 mice received 15 Gray of (hemi)-thorax irradiation in a single dose. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected at defined time points post-irradiation for the determination of apoptosis, microvascular injury, and histological and immunohistochemical analyses.
Higher albumin levels and increased apoptosis were detected in the BALF 21 days after irradiation, indicative for delayed damage to resident cells. Irradiation also induced time-dependent changes in the BALF cytokine profile, the recruitment of activated T-cells into the lung and the formation of lipid-loaded resident cells. Lung fibrosis occurred earlier in RAG-2(-/-) mice, which lack mature T and B cells, compared to WT mice.
Thorax irradiation triggers a delayed disturbance of tissue integrity and lipid metabolism in the lung. Activated T-lymphocytes infiltrating the lung tissue upon thorax irradiation participate in the protection of the lung from radiation-induced fibrosis.
肺炎和纤维化是胸部或全身照射的剂量限制副作用。深入了解潜在的机制是开发有效辐射防护策略的前提。在这里，我们描述了辐射诱导的肺疾病小鼠模型中固有和免疫细胞的行为。
野生型（WT）或 RAG-2 缺陷 C57BL/6 小鼠单次接受 15 Gray 的（半）胸部照射。照射后在特定时间点收集支气管肺泡灌洗液（BALF）和肺组织，以确定细胞凋亡、微血管损伤、组织学和免疫组织化学分析。
照射后 21 天，BALF 中的白蛋白水平升高和凋亡增加，表明固有细胞发生迟发性损伤。照射还导致 BALF 细胞因子谱、激活的 T 细胞向肺部募集以及富含脂质的固有细胞形成的时间依赖性变化。与 WT 小鼠相比，缺乏成熟 T 和 B 细胞的 RAG-2(-/-) 小鼠的肺纤维化发生更早。
胸部照射会引发肺部组织完整性和脂质代谢的延迟紊乱。在胸部照射时浸润肺组织的活化 T 淋巴细胞参与了对肺免受辐射诱导的纤维化的保护。
